FDG-C Duo Application Manual

GE Healthcare
Original User Instructions
FASTlabTM 2 synthesizer
FDG Duo citrate

Application Manual
GE Healthcare FDG Duo citrate Application Manual
DOC1648601 FASTlab 2 – Version 4
Warranty and liability
GE Healthcare (GEHC) does not accept liability for injury to personnel or damage to equipment that
may result from misuse of this equipment, failure to observe the hazard notices contained in this
manual, or failure to observe federal, state and/or local regulations.
Whilst every effort has been made to ensure the technical accuracy of this manual, the information
contained herein is subject to change without notice. GEHC makes no warranty of any kind with
regard to this material.
GEHC shall not be liable for errors contained herein, or for incidental or consequential damages
arising from the use of the equipment described in this manual.
Internet updates: Common Documentation library
FASTlab manuals are available for viewing and downloading via internet.
Please check regularly the GE Common Documentation Library (CDL) website for updates:
- Go to
http://apps.gehealthcare.com/servlet/ClientServlet?REQ=Enter%2bDocumentation%2bLib
rary.
- Click the “Radiopharmacy” menu entry.
- Select “FASTlab 2” in the Radiopharmacy Product drop down list.
- Select “All” in the Manual Types drop down list.
- Click “Search” at the bottom of the screen.
2 /53
ПРЕДУПРЕЖДЕНИЕ Това упътване за работа е налично само на английски език.

(BG) • Ако доставчикът на услугата на клиента изиска друг език, задължение на клиента
е да осигури превод.
• Не използвайте оборудването, преди да сте се консултирали и разбрали
упътването за работа.
• Неспазването на това предупреждение може да доведе до нараняване на
доставчика на услугата, оператора или пациентa в резултат на токов удар,
механична или друга опасност.
警告本维修手册仅提供英文版本。
(ZH-CN) • 如果客户的维修服务人员需要非英文版本，则客户需自行提供翻译服务。
• 未详细阅读和完全理解本维修手册之前，不得进行维修。
• 忽略本警告可能对维修服务人员、操作人员或患者造成电击、机械伤害或其他形
式的伤害。
警告本服務手冊僅提供英文版本。
(ZH-HK) • 倘若客戶的服務供應商需要英文以外之服務手冊，客戶有責任提供翻譯服務。
• 除非已參閱本服務手冊及明白其內容，否則切勿嘗試維修設備。
• 不遵從本警告或會令服務供應商、網絡供應商或病人受到觸電、機械性或其他的
危險。
警告本維修手冊僅有英文版。
(ZH-TW) • 若客戶的維修廠商需要英文版以外的語言，應由客戶自行提供翻譯服務。
• 請勿試圖維修本設備，除非您已查閱並瞭解本維修手冊。
• 若未留意本警告，可能導致維修廠商、操作員或病患因觸電、機械或其他危險而
受傷。
UPOZORENJE Ovaj servisni priručnik dostupan je na engleskom jeziku.

(HR) • Ako davatelj usluge klijenta treba neki drugi jezik, klijent je dužan osigurati prijevod.
• Ne pokušavajte servisirati opremu ako niste u potpunosti pročitali i razumjeli ovaj
servisni priručnik.
• Zanemarite li ovo upozorenje, može doći do ozljede davatelja usluge, operatera ili
pacijenta uslijed strujnog udara, mehaničkih ili drugih rizika.
VÝSTRAHA Tento provozní návod existuje pouze v anglickém jazyce.

(CS) • V případě, že externí služba zákazníkům potřebuje návod v jiném jazyce, je zajištění
překladu do odpovídajícího jazyka úkolem zákazníka.
• Nesnažte se o údržbu tohoto zařízení, aniž byste si přečetli tento provozní návod a
pochopili jeho obsah.
• V případě nedodržování této výstrahy může dojít k poranění pracovníka prodejního
servisu, obslužného personálu nebo pacientů vlivem elektrického proudu, respektive
vlivem mechanických či jiných rizik.
ADVARSEL Denne servicemanual findes kun på engelsk.

(DA) • Hvis en kundes tekniker har brug for et andet sprog end engelsk, er det kundens ansvar
at sørge for oversættelse.
• Forsøg ikke at servicere udstyret uden at læse og forstå denne servicemanual.
• Manglende overholdelse af denne advarsel kan medføre skade på grund af elektrisk
stød, mekanisk eller anden fare for teknikeren, operatøren eller patienten.
3 /53
WAARSCHUWING Deze onderhoudshandleiding is enkel in het Engels verkrijgbaar.

(NL) • Als het onderhoudspersoneel een andere taal vereist, dan is de klant verantwoordelijk
voor de vertaling ervan.
• Probeer de apparatuur niet te onderhouden alvorens deze onderhoudshandleiding
werd geraadpleegd en begrepen is.
• Indien deze waarschuwing niet wordt opgevolgd, zou het onderhoudspersoneel, de
operator of een patiënt gewond kunnen raken als gevolg van een elektrische schok,
mechanische of andere gevaren.
WARNING
(EN) This service manual is available in English only.
• If a customer's service provider requires a language other than english, it is the
customer's responsibility to provide translation services.
• Do not attempt to service the equipment unless this service manual has been
consulted and is understood.
• Failure to heed this warning may result in injury to the service provider, operator or
patient from electric shock, mechanical or other hazards.
HOIATUS
See teenindusjuhend on saadaval ainult inglise keeles
(ET)
• Kui klienditeeninduse osutaja nõuab juhendit inglise keelest erinevas keeles, vastutab
klient tõlketeenuse osutamise eest.
• Ärge üritage seadmeid teenindada enne eelnevalt käesoleva teenindusjuhendiga
tutvumist ja sellest aru saamist.
• Käesoleva hoiatuse eiramine võib põhjustada teenuseosutaja, operaatori või patsiendi
vigastamist elektrilöögi, mehaanilise või muu ohu tagajärjel.
VAROITUS
Tämä huolto-ohje on saatavilla vain englanniksi.
(FI)
• Jos asiakkaan huoltohenkilöstö vaatii muuta kuin englanninkielistä materiaalia,
tarvittavan käännöksen hankkiminen on asiakkaan vastuulla.
• Älä yritä korjata laitteistoa ennen kuin olet varmasti lukenut ja ymmärtänyt tämän
huolto-ohjeen.
• Mikäli tätä varoitusta ei noudateta, seurauksena voi olla huoltohenkilöstön, laitteiston
käyttäjän tai potilaan vahingoittuminen sähköiskun, mekaanisen vian tai muun
vaaratilanteen vuoksi.
ATTENTION
Ce manuel d’installation et de maintenance est disponible uniquement en anglais.
(FR)
• Si le technicien d'un client a besoin de ce manuel dans une langue autre que l'anglais,
il incombe au client de le faire traduire.
• Ne pas tenter d'intervenir sur les équipements tant que ce manuel d’installation et de
maintenance n'a pas été consulté et compris.
• Le non-respect de cet avertissement peut entraîner chez le technicien, l'opérateur ou le
patient des blessures dues à des dangers électriques, mécaniques ou autres.
WARNUNG
(DE) Diese Serviceanleitung existiert nur in englischer Sprache.
• Falls ein fremder Kundendienst eine andere Sprache benötigt, ist es Aufgabe des
Kunden für eine entsprechende Übersetzung zu sorgen.
• Versuchen Sie nicht diese Anlage zu warten, ohne diese Serviceanleitung gelesen und
verstanden zu haben.
• Wird diese Warnung nicht beachtet, so kann es zu Verletzungen des
Kundendiensttechnikers, des Bedieners oder des Patienten durch Stromschläge,
mechanische oder sonstige Gefahren kommen.
ΠΡΟΕΙΔΟΠΟΙΗΣΗ
Το παρόν εγχειρίδιο σέρβις διατίθεται μόνο στα αγγλικά.
(EL)
• Εάν ο τεχνικός σέρβις ενός πελάτη απαιτεί το παρόν εγχειρίδιο σε γλώσσα εκτός των
αγγλικών, αποτελεί ευθύνη του πελάτη να παρέχει τις υπηρεσίες μετάφρασης.
• Μην επιχειρήσετε την εκτέλεση εργασιών σέρβις στον εξοπλισμό αν δεν έχετε
συμβουλευτεί και κατανοήσει το παρόν εγχειρίδιο σέρβις.
• Αν δεν προσέξετε την προειδοποίηση αυτή, ενδέχεται να προκληθεί τραυματισμός
στον τεχνικό σέρβις, στο χειριστή ή στον ασθενή από ηλεκτροπληξία, μηχανικούς ή
άλλους κινδύνους.
4 /53
FIGYELMEZTETÉS Ezen karbantartási kézikönyv kizárólag angol nyelven érhető el.

(HU) • Ha a vevő szolgáltatója angoltól eltérő nyelvre tart igényt, akkor a vevő felelőssége a
fordítás elkészíttetése.
• Ne próbálja elkezdeni használni a berendezést, amíg a karbantartási kézikönyvben
leírtakat nem értelmezték.
• Ezen figyelmeztetés figyelmen kívül hagyása a szolgáltató, működtető vagy a beteg
áramütés, mechanikai vagy egyéb veszélyhelyzet miatti sérülését eredményezheti.
AÐVÖRUN Þessi þjónustuhandbók er aðeins fáanleg á ensku.

(IS) • Ef að þjónustuveitandi viðskiptamanns þarfnast annas tungumáls en ensku, er það
skylda viðskiptamanns að skaffa tungumálaþjónustu.
• Reynið ekki að afgreiða tækið nema að þessi þjónustuhandbók hefur verið skoðuð og
skilin.
• Brot á sinna þessari aðvörun getur leitt til meiðsla á þjónustuveitanda, stjórnanda eða
sjúklings frá raflosti, vélrænu eða öðrum áhættum.
AVVERTENZA Il presente manuale di manutenzione è disponibile soltanto in lingua inglese.

(IT) • Se un addetto alla manutenzione richiede il manuale in una lingua diversa, il cliente è
tenuto a provvedere direttamente alla traduzione.
• Procedere alla manutenzione dell'apparecchiatura solo dopo aver consultato il
presente manuale ed averne compreso il contenuto.
• Il mancato rispetto della presente avvertenza potrebbe causare lesioni all'addetto alla
manutenzione, all'operatore o ai pazienti provocate da scosse elettriche, urti meccanici
o altri rischi.
このサービスマニュアルには英語版しかありません。
(JA) • サービスを担当される業者が英語以外の言語を要求される場合、翻訳作業はその
業者の責任で行うものとさせていただきます。
• このサービスマニュアルを熟読し理解せずに、装置のサービスを行わないでくだ
さい。
• この警告に従わない場合、サービスを担当される方、操作員あるいは患者さん
が、感電や機械的又はその他の危険により負傷する可能性があります。
경고 본 서비스 매뉴얼은 영어로만 이용하실 수 있습니다.

(KO) • 고객의 서비스 제공자가 영어 이외의 언어를 요구할 경우, 번역 서비스를
제공하는 것은 고객의 책임입니다.
• 본 서비스 매뉴얼을 참조하여 숙지하지 않은 이상 해당 장비를 수리하려고
시도하지 마십시오.
• 본 경고 사항에 유의하지 않으면 전기 쇼크, 기계적 위험, 또는 기타 위험으로
인해 서비스 제공자, 사용자 또는 환자에게 부상을 입힐 수 있습니다.
BRĪDINĀJUMS Šī apkopes rokasgrāmata ir pieejama tikai angļu valodā.

(LV) • Ja klienta apkopes sniedzējam nepieciešama informācija citā valodā, klienta
pienākums ir nodrošināt tulkojumu.
• Neveiciet aprīkojuma apkopi bez apkopes rokasgrāmatas izlasīšanas un saprašanas.
• Šī brīdinājuma neievērošanas rezultātā var rasties elektriskās strāvas trieciena,
mehānisku vai citu faktoru izraisītu traumu risks apkopes sniedzējam, operatoram vai
pacientam.
ĮSPĖJIMAS Šis eksploatavimo vadovas yra tik anglų kalba.

(LT) • Jei kliento paslaugų tiekėjas reikalauja vadovo kita kalba – ne anglų, suteikti vertimo
paslaugas privalo klientas.
• Nemėginkite atlikti įrangos techninės priežiūros, jei neperskaitėte ar nesupratote šio
eksploatavimo vadovo.
• Jei nepaisysite šio įspėjimo, galimi paslaugų tiekėjo, operatoriaus ar paciento
sužalojimai dėl elektros šoko, mechaninių ar kitų pavojų.
5 /53
ADVARSEL Denne servicehåndboken finnes bare på engelsk.

(NO) • Hvis kundens serviceleverandør har bruk for et annet språk, er det kundens ansvar å
sørge for oversettelse.
• Ikke forsøk å reparere utstyret uten at denne servicehåndboken er lest og forstått.
• Manglende hensyn til denne advarselen kan føre til at serviceleverandøren, operatøren
eller pasienten skades på grunn av elektrisk støt, mekaniske eller andre farer.
OSTRZEŻENIE Niniejszy podręcznik serwisowy dostępny jest jedynie w języku angielskim.

(PL) • Jeśli serwisant klienta wymaga języka innego niż angielski, zapewnienie usługi
tłumaczenia jest obowiązkiem klienta.
• Nie próbować serwisować urządzenia bez zapoznania się z niniejszym podręcznikiem
serwisowym i zrozumienia go.
• Niezastosowanie się do tego ostrzeżenia może doprowadzić do obrażeń serwisanta,
operatora lub pacjenta w wyniku porażenia prądem elektrycznym, zagrożenia
mechanicznego bądź innego.
AVISO Este manual de assistência técnica encontra-se disponível unicamente em inglês.

(PT-BR) • Se outro serviço de assistência técnica solicitar a tradução deste manual, caberá ao
cliente fornecer os serviços de tradução.
• Não tente reparar o equipamento sem ter consultado e compreendido este manual de
assistência técnica.
• A não observância deste aviso pode ocasionar ferimentos no técnico, operador ou
paciente decorrentes de choques elétricos, mecânicos ou outros.
ATENÇÃO Este manual de assistência técnica só se encontra disponível em inglês.

(PT-PT) • Se qualquer outro serviço de assistência técnica solicitar este manual noutro idioma, é
da responsabilidade do cliente fornecer os serviços de tradução.
• Não tente reparar o equipamento sem ter consultado e compreendido este manual de
assistência técnica.
• O não cumprimento deste aviso pode colocar em perigo a segurança do técnico, do
operador ou do paciente devido a choques eléctricos, mecânicos ou outros.
ATENŢIE Acest manual de service este disponibil doar în limba engleză.

(RO) • Dacă un furnizor de servicii pentru clienţi necesită o altă limbă decât cea engleză, este
de datoria clientului să furnizeze o traducere.
• Nu încercaţi să reparaţi echipamentul decât ulterior consultării şi înţelegerii acestui
manual de service.
• Ignorarea acestui avertisment ar putea duce la rănirea depanatorului, operatorului sau
pacientului în urma pericolelor de electrocutare, mecanice sau de altă natură.
ОСТОРОЖНО! Данное руководство по техническому обслуживанию представлено только на

(RU) английском языке.
• Если сервисному персоналу клиента необходимо руководство не на английском, а
на каком-то другом языке, клиенту следует самостоятельно обеспечить перевод.
• Перед техническим обслуживанием оборудования обязательно обратитесь к
данному руководству и поймите изложенные в нем сведения.
• Несоблюдение требований данного предупреждения может привести к тому, что
специалист по техобслуживанию, оператор или пациент получит удар
электрическим током, механическую травму или другое повреждение.
UPOZORENJE Ovo servisno uputstvo je dostupno samo na engleskom jeziku.

(SR) • Ako klijentov serviser zahteva neki drugi jezik, klijent je dužan da obezbedi prevodilačke
usluge.
• Ne pokušavajte da opravite uređaj ako niste pročitali i razumeli ovo servisno uputstvo.
• Zanemarivanje ovog upozorenja može dovesti do povređivanja servisera, rukovaoca ili
pacijenta usled strujnog udara ili mehaničkih i drugih opasnosti.
6 /53
UPOZORNENIE Tento návod na obsluhu je k dispozícii len v angličtine.

(SK) • Ak zákazníkov poskytovateľ služieb vyžaduje iný jazyk ako angličtinu, poskytnutie
prekladateľských služieb je zodpovednosťou zákazníka.
• Nepokúšajte sa o obsluhu zariadenia, kým si neprečítate návod na obluhu a
neporozumiete mu.
• Zanedbanie tohto upozornenia môže spôsobiť zranenie poskytovateľa služieb,
obsluhujúcej osoby alebo pacienta elektrickým prúdom, mechanické alebo iné
ohrozenie.
ATENCION Este manual de servicio sólo existe en inglés.

(ES) • Si el encargado de mantenimiento de un cliente necesita un idioma que no sea el
inglés, el cliente deberá encargarse de la traducción del manual.
• No se deberá dar servicio técnico al equipo, sin haber consultado y comprendido este
manual de servicio.
• La no observancia del presente aviso puede dar lugar a que el proveedor de servicios,
el operador o el paciente sufran lesiones provocadas por causas eléctricas, mecánicas
o de otra naturaleza.
VARNING Den här servicehandboken finns bara tillgänglig på engelska. .

(SV) • Om en kunds servicetekniker har behov av ett annat språk än engelska, ansvarar
kunden för att tillhandahålla översättningstjänster.
• Försök inte utföra service på utrustningen om du inte har läst och förstår den här
servicehandboken.
• Om du inte tar hänsyn till den här varningen kan det resultera i skador på
serviceteknikern, operatören eller patienten till följd av elektriska stötar, mekaniska
faror eller andra faror.
OPOZORILO Ta servisni priročnik je na voljo samo v angleškem jeziku.

(SL) • Če ponudnik storitve stranke potrebuje priročnik v drugem jeziku, mora stranka
zagotoviti prevod.
• Ne poskušajte servisirati opreme, če tega priročnika niste v celoti prebrali in razumeli.
• Če tega opozorila ne upoštevate, se lahko zaradi električnega udara, mehanskih ali
drugih nevarnosti poškoduje ponudnik storitev, operater ali bolnik.
DİKKAT Bu servis kılavuzunun sadece ingilizcesi mevcuttur.

(TR) • Eğer müşteri teknisyeni bu kılavuzu ingilizce dışında bir başka lisandan talep ederse,
bunu tercüme ettirmek müşteriye düşer.
• Servis kılavuzunu okuyup anlamadan ekipmanlara müdahale etmeyiniz.
• Bu uyarıya uyulmaması, elektrik, mekanik veya diğer tehlikelerden dolayı teknisyen,
operatör veya hastanın yaralanmasına yol açabilir.
7 /53
VERSION HISTORY
Version Date Reason for change
1 OCT 2015 First release of the document
Correction of the text in section 10.5.1 by changing
2 JUN 2016 mannose triflate into NaOH and adding the point
regarding reagents quality.
3 May 2017 Update of company address.
Update regarding contents of tracer package ( refer
4 Oct 2019
Chapter.4)
8 /53
ACRONYMS & GLOSSARY

°C Celcius degree
FDG 2-[18F]fluoro-2-deoxy-D-glucose
FID Flame ionization detector
FTAG 2-[18F]-fluoro-1,3,4,6-tetra-O-acetyl-D-glucose
GC Gas Chromatophy
GE General Electric
GEHC General Electric Healthcare
MeCN Acetonitrile
MSDS Material Safety Data Sheet
mL Milliliter
mm Millimeter
mg Milligram
min Minute
µL Microliter
µg Microgram
µS/cm microsiemens/centimeter
N Normality
NaOH Sodium Hydroxide
18O (-water) Oxygen istope 18 (enriched water)
PLC Programmable Logical Controler
pH Potentiel hydrogene
ppm Part per million
QC Quality Control
QMA (cartridge) Quaternary methyl ammonium (cartridge)
S3 Syringe 3 (the right hand syringe of the cassette)
TLC Thin Layer Chromatography
9 /53
Contents
VERSION HISTORY 8
ACRONYMS & GLOSSARY 9
CHAPTER 1 - INTRODUCTION 12
CHAPTER 2 - RADIOPHARMACEUTICAL REQUIREMENTS 13
CHAPTER 3 - FDG DUO CITRATE CASSETTE 14
3-1 THE FDG DUO CITRATE CASSETTE 14
3-2 REAGENTS 15
3-3 CARTRIDGES 16
CHAPTER 4 - DESCRIPTION ON THE CHEMICAL PROCESS 17
4-1 PREPARATION OF THE FLUORINATING AGENT 18
4-2 SYNTHESIZER AND CASSETTE TEST 18
4-3 PRELIMINARY STEPS 18
4-4 ENRICHED WATER RECOVERY AND ELUTION 19
4-5 18F AZEOTROPIC DRYING 19
4-6 LABELLING THE PRECURSOR 19
4-7 PRELIMINARY FTAG PURIFICATION 19
4-8 HYDROLYSIS ON SOLID SUPPORT 20
4-9 PH AND OSMOLALITY ADJUSTMENT 21
4-10 PURIFICATION AND TRANSFER 21
4-11 CASSETTE RINSING 21
4-12 GENERAL INFORMATION FOR ONE PRODUCTION 22
CHAPTER 5 - OPERATING TWO PRODUCTIONS ON THE SAME CASSETTE 23
5-1 INTRODUCTION 23
5-2 INSTALLATION OF THE SIDE HOOK FOR THE WATER BAG ON THE FASTLAB 2 SYNTHESIZER 23
5-2-1 Assembly of the side hook 23
5-3 MOUNT THE FDG DUO CITRATE CASSETTE ON THE FASTLAB 2 SYNTHESIZER 25
5-4 THE WORKFLOW ADVANCEMENT 26
5-5 THE CLEANING PROCESS 26
5-6 THE WAITING TIME 27
5-7 THE SECOND PRODUCTION ON THE FDG DUO CITRATE CASSETTE 28
5-8 FDG DUO CITRATE CASSETTE REMOVAL AFTER WORKFLOW 28
5-9 DISCARDING OF THE CASSETTE 29
5-10 SPECIFIC TROUBLESHOOTING 29
5-10-1 Liquid is coming out of the rear of the FASTlab module 29
5-10-2 I don’t see the cassette rinsing checkbox 29
5-10-3 I can’t start the second production 30
5-10-4 I ended the workflow after the first production, and then removed the cassette without cleaning/emptying
it. Can I reuse the cassette for another first production another day? 30
CHAPTER 6 - CALIBRATION OF THE RADIOACTIVITY DETECTORS 31

6-1 CALIBRATION OF THE FIRST PRODUCTION 31
6-2 CALIBRATION OF THE SECOND PRODUCTION 33
CHAPTER 7 - REPORTS 34
10 /53
7-1 INTRODUCTION 34
7-2 GENERAL INFORMATION 37
7-2-1 Process report 38
7-2-2 Yield summary 38
7-2-3 Activity trending 39
7-2-4 Trending 39
7-2-5 Log 39
7-2-6 Operator comment 39
7-2-7 Operator signature 39
7-2-8 Responsible signature 40
7-3 CASSETTE RINSING REPORT 40
CHAPTER 8 - FDG CITRATE QUALITY CONTROL 42
CHAPTER 9 - FDG DUO CITRATE CASSETTE REMOVAL 44
9-1 FDG DUO CITRATE CASSETTE REMOVAL AFTER PRODUCTION 44
9-2 DISCARDING OF THE CASSETTE 44
CHAPTER 10 - TROUBLESHOOTING 45
10-1 INTRODUCTION AND PRELIMINARY WARNING 45
10-2 LOW YIELD 45
10-2-1 Insufficient radioactivity trapping on the QMA cartridge 46
10-2-2 QMA elution problem 47
10-2-3 The radioactivity was not trapped properly on the tC18 cartridge before the hydrolysis 47
10-2-4 Hydrolysis issue 48
10-2-5 Radiochemistry problem (Labelling or drying) 48
10-3 FLUCTUATING YIELDS 49
10-4 LOW, OR FLUCTUATING, VOLUME OF FDG IN THE FINAL SOLUTION 49
10-5 THE QUALITY OF THE FINAL PRODUCT DOES NOT MEET THE PHARMACEUTICAL REQUIREMENTS 50
10-5-1 The pH of the product is too high 50
10-5-2 The pH of the product is too low 50
10-5-3 The FDG solution is not clear and colourless 51
10-5-4 There are unknown radioactive impurities in the FDG solution 51
10-5-5 The amount of residual free 18F ions is abnormally high 51
10-5-6 The amount of acetonitrile is too high 51
10-5-7 The amount of ethanol is too high 52
11 /53
CHAPTER 1 - INTRODUCTION
The FASTlabTM 2 is a compact automated system that converts externally produced radio-isotopes
(from cyclotron) into radiochemicals ready for further processing and quality control. This is
achieved thanks to single-use consumables, called cassettes, which the FASTlab 2 actuates
following step-by-step sequences. The radioactive tracers produced by the FASTlab 2 are usable in
Positron Emission Tomography (PET).
In addition to the global documentation package “FASTlab 2 – User Documentation” described here
below, each tracer cassette has its own manual called “Application manual”. The application
manuals describe the specific cassette items such as cassette configuration, set up, residual
radioactivity, specific radioactivity detectors calibration procedure, the general chemical process
and a tracer-specific trouble shooting.
This “FASTlab 2 – FDG Duo citrate Application Manual” contains the necessary information about
the specific FDG Duo citrate cassette and can be used to assist the operator during FDG Duo citrate
synthesis and troubleshooting operation.
The “FASTlab 2 – User Documentation” package consist of four manuals:
- FASTlab 2 – Operator Manual

It contains the necessary information to assist the operator for a routine production using
the FASTlab 2: a description of the equipment, a description of the control tools and displays
available to the user, the calibration procedure for the radioactivity detectors, and all the
required operating instructions.
- FASTlab 2 – Service Manual

It contains all the information related to servicing and maintenance of the FASTlab 2: a
description of the maintenance mode, troubleshooting information, maintenance checks
and frequencies, etc.
- FASTlab 2 – Pre-Installation and Installation Manual

It contains information about the site requirements and all the instructions to support a
proper installation of the FASTlab 2.
- FASTlab 2 – Health, Safety and Regulatory Manual

It contains the health, safety and regulatory information and instructions such as cautions,
warnings, potential dangers, safety labels, marking, etc.
The FASTlab 2 can also be used as a tracer development tool, providing the purchase of a specific
license. The “FASTlab 2 – Developer Manual” contains all the necessary information to assist the
developer elaborating new sequences using the FASTlab 2.
12 /53
CHAPTER 2 - RADIOPHARMACEUTICAL REQUIREMENTS

All personnel must read this chapter and be fully aware of its contents before operating the FASTlab
2.
All personnel associated with the operation and maintenance of the FASTlab 2 must be
appropriately qualified for radiopharmaceutical production and must be made familiar with the use
of the FASTlab 2.
Operating personnel must be informed of all applicable health and safety regulations.
The FASTlab 2 is not shielded. It must be operated within a hot cell with sufficient shielding to be
compliant with local radioprotection regulations. The waste bottle must be shielded, even when
located in the hot cell. It is mandatory to close the door of the hot cell and to keep the door closed
during transfer of the radioactive species from the cyclotron to the FASTlab 2, and during the whole
synthesis.
After use, and although rinsed, the disposable cassette contains residues of radioactive material.
Do not remove the cassette before sufficient decay. The cassette contaminated with radioactive
material must be discarded in compliance with local radiopharmaceutical regulations. Note that
the cassette can also be contaminated with long half-life radioactive target impurities. Measure the
remaining radioactivity on the cassette in order to ensure proper storage until sufficient decay.
It is mandatory to use a radiation monitoring system inside the hot cell in order to assess the level
of radioactivity inside the enclosure before any potential opening. It should be noted that the
purpose of the embedded radioactivity detectors from the FASTlab 2 is to follow the radiochemical
process only. Under no circumstances can they be used to assess the radioactivity level inside the
hot cell.
The use of Personal Protective Equipment (PPE) such as safety glasses, gloves and a lab coat is
mandatory when handling the contaminated cassette or when operating the FASTlab 2 after a hot
synthesis. Nitrile gloves are highly recommended when handling contaminated material, instead of
latex which is more porous.
The operator should wear personal dosimeter at any time while handling or working with
radioactive products.
For more information regarding health and safety considerations while operating the FASTlab 2,
please refer to the “FASTlab 2 – Health, Safety and Regulatory Manual” supplied as a part of the
global documentation package “FASTlab 2 – User Documentation”.
Proper Quality Control must be conducted on each batch of tracer solution produced using the
FASTlab 2, according to the local radiopharmaceutical laws and regulations.
Any and all radiopharmaceutical production with the FASTlab 2 is the sole responsibility of the
qualified radiopharmacist, and must be conform to all local laws and regulations.
13 /53
CHAPTER 3 - FDG DUO CITRATE CASSETTE

3-1 The FDG Duo citrate cassette
The FDG Duo citrate production using the FASTlab 2 synthesizer is carried out in a disposable fluid
pathway called the FDG Duo citrate cassette.
The FDG Duo citrate cassette is specially designed to allow the production of two consecutive
batches of FDG citrate with one cassette with no need to open the hot cell door between the two
productions.
Those two productions are performed sequentially during one “workflow” consisting of the first run,
an operator dependant waiting step (up to 26 hours – software restricted), and then the second run.
The Main steps of the entire workflow of FDG production with the FDG Duo citrate cassette are:
• A first chemical process that lead to the first batch of FDG (RUN1) automatically followed
by a cleaning process that ensures that the cassette is of a proper status to start a
second FDG run
• a waiting time that allows the customer to be ready for the second run
• a second FDG production (RUN2)
• and an optional cassette rinsing that reduces as much as possible the residual activity on
the cassette in order to reduce the dose exposure to the operator
This means that if the FASTlab 2 synthesizer is turned OFF, or if a waiting time of more than 26 hours
separates the two productions, the second production cannot be carried on as the workflow is
interrupted.
Important note: If the workflow is interrupted for any reason (failure of the first run, too long waiting
time or removal of the cassette…), the process is automatically stopped and the cassette MUST be
discarded. The cassette cannot be used to run the second production anymore.
The FDG Duo citrate cassette must be replaced between each workflow (i.e. two productions of FDG
citrate consecutively with one cassette) to ensure clean and reproducible operation for every FDG
citrate batch production.
Important note: For ease of writing, the term workflow will be used in this manual to refer to the
complete process of the first production of FDG citrate with the cassette + the waiting time + the
second production of FDG citrate. The term production will be used to name the making of one
batch of FDG citrate.
The disposable cassette is an original GEHC design. It includes a 25-valves stopcock manifold, a
reaction vessel, two 6 mL syringes, one 1 mL syringe, connections for incoming and outgoing fluids,
spikes for the connection with the reagent vials, a larger spike for the connection with the water
bag, and various solid phase extraction cartridges.
The FDG Duo citrate cassette package can only be purchased from GEHC and includes a hard
plastic sheet containing the cassette itself and a vent filter within a double sealed plastic bag. In
addition, a 250 mL water bottle and certificates are included in the FDG Duo citrate cassette
package.
Important note: The cassette pack does not contain the outlet product filters. It is absolutely
mandatory to use a 0.2 µm sterile filter between each of the cassette outlet line and the FDG
collection vials.
14 /53
FIGURE 3-1: The FDG Duo citrate cassette, the nitrogen vent filter and the 250 mL water bag
3-2 Reagents
Six reagent vials are used in the FDG Duo citrate cassette. The eluent, ethanol, mannose triflate
precursor, sodium hydroxide, acetonitrile and citrate buffer are placed into the six reagent barrels
on the manifold. Water is also used but is not included in the cassette slots. The water bag is
separated from the cassette in the packaging.
Please find a brief description and safety hazards of the reagents in the TABLE I below:
Mannose Sodium Citrate

Eluent Ethanol Acetonitrile
triflate hydroxide buffer
FIGURE 3-2: Identification of the reagents used in the FDG Duo citrate cassette
TABLE I: Identification of the reagents used in the FDG Duo citrate cassette
Reagent Container Colour code Amount Hazards
Eluent mixture
containing:
- Kryptofix ® 3 mL glass vial –
- Potassium capped – 11 mm Dark brown 1.4 mL
carbonate neck
- Acetonitrile Flammable – Corrosive - Toxic
- Water
3 mL glass vial –
Ethanol capped – 11 mm Blue 2.5 mL
neck
Flammable
15 /53
5 mL glass vial –
Mannose triflate
capped – 13 mm Orange 4.0 mL
in MeCN
neck
Flammable - Toxic
5 mL glass vial –
Sodium hydroxide capped – 13 mm Red 4.2 mL
neck
Corrosive
5 mL glass vial –
Acetonitrile capped – 13 mm Green 4.2 mL
neck
Toxic - Flammable
5 mL glass vial –
Citrate buffer capped – 13 mm Silver 4.3 mL
neck
Corrosive - Toxic
Important note: For complete information regarding safety and hazards of the reagents above-
mentioned, please refer to the MSDS of the cassette found in the cassette packaging, and the
“FASTlab 2 – Health, Safety and Regulatory Manual”
3-3 Cartridges
Six cartridges are used on the FDG Duo citrate cassette: two QMA (light blue ring) cartridges to trap
the incoming radioactivity, one tC18 environmental cartridge (red ring), one tC18 plus (red ring) and
two Alumina N (light green ring) cartridges.
The tC18 cartridges are rinsed between the two productions and used twice. The other cartridges
have been doubled up and one cartridge is used for one production, as their natures make them
more complex to rinse properly.
tC18
QMA Alumina N tC18 plus
environmental
FIGURE 3-3: Identification of the reagents used in the FDG Duo citrate cassette
16 /53
CHAPTER 4 - DESCRIPTION ON THE CHEMICAL PROCESS

The production of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) using the FASTlab 2 synthesizer is
performed using the method described below.
One production takes about 30 minutes between the entry of the radioactivity in the synthesizer,
and the end of the delivery of the FDG to the collection vial. The resulting FDG solution is clear,
colourless and lightly acidic. It is ready for Quality Control. Please note that the second production
is slightly shorter (25 minutes) as the preliminary steps must not be carried out again.
The chemical process is the same for both production performed with the FDG Duo citrate cassette.
For information relating to the process specific to the production of two batches in a row with the
same cassette, please refer to the Chapter 5 of this manual.
Important note: The FDG citrate tracer data package comes by default with several synthesis
sequences installed. The small differences between the sequences are adaptation to specific set-
up. It is recommended to approve only one sequence in the “synthesis sequence management”
menu (see the “Pre-installation and Installation manual”).
Tracer Package 1.0.0.1 contains:

Product Volume Name of the sequence Description
GE_duoFDGc_PETCS020FL_A
GE_duoFDGc_PETCS020FL_B
Large target volume sequence
to be used in case more than 5
mL if enriched water must be
transferred from cyclotron (see
GE_duoFDGc_LTV_PETCS020FL_A the “selection of synthesis”
section of the Operator
manual. The vacuum set point
at “Ready to receive activity” is
-600 mbar.
22 mL mL if enriched water must be
GE_duoFDGc_LTV_PETCS020FL_B the “selection of synthesis”
-600 mbar.
GE_duoFDGc_LTV400_PETCS020FL_A the “selection of synthesis”
-400 mbar.
17 /53

22 mL GE_duoFDGc_LTV400_PETCS020FL_B the “selection of synthesis”
-400 mbar.
4-1 Preparation of the fluorinating agent

The radionuclide is produced in the form of fluoride ions by bombardment of [18O]-water with
accelerated protons. The amount of [18F]-activity recovered usually ranges between 600 mCi and
20 Ci (22 and 740 GBq).
WARNING – For bombardment within the cyclotron target, the use of [18O]-water enriched above
95% is recommended. Commercially available [18O]-water does not usually require further
purification. Following irradiation, the irradiated [18O]-water should be colourless and free of any
visible contamination, with conductivity below 10 µS/cm. GE Healthcare makes no guarantee
regarding the presence in the final product of radio contaminants from the target, because such
impurities are site related (contributing factors: cyclotron and target maintenance, quality of
enriched water and irradiation parameters).
WARNING – GE Healthcare makes no guarantee regarding the performance of the FDG Duo citrate
process if the cyclotron is not operated and maintained following supplier specifications.
4-2 Synthesizer and cassette test

Those two tests can be performed at the beginning of a workflow to verify the integrity of both the
FASTlab 2 synthesizer and the FDG Duo citrate cassette mounted on it. Please refer to the
corresponding sections of the “FASTlab 2 – Operator Manual” for more information on these tests.
Important note: The water bag must be manually pierced by the operator before the FDG Duo
process. This must exceptionally be performed AFTER the cassette test to avoid potential
contamination of the manifold during the cassette test. Please refer to the Chapter 5 of this manual
for more information on the cassette mounting procedure.
4-3 Preliminary steps

The preliminary steps of the production of FDG citrate can be started during the irradiation. These
first steps are performed before transfer of the radioactivity into the synthesizer. They consist in:
- Punching the reagent vials on the spikes (only for the first production)
- Priming the water bottle tubing (only for the first production)
- Pressurizing the reagent vials
- Conditioning the tC18 cartridges
The operator is informed as soon as the synthesizer is ready to receive the irradiated water by
means of a message displayed on the screen.
Duration of this step: ± 5 minutes
18 /53
4-4 Enriched water recovery and elution

After bombardment the irradiated [18O]-water is transferred into the FASTlab 2 synthesizer. The
radioactive solution is passed through one of the anion exchange cartridge (QMA) on which the
[18F]-fluoride ions are trapped while the enriched water is recovered for recycling. Depending on the
sequence selected by the operator, this transfer can be direct (the radioactivity is transferred from
the cyclotron directly onto the QMA via the radioactivity plunger) or indirect (the radioactivity is
transferred into the conical reservoir, and then passed through the QMA after all the radioactivity
has been received in the reservoir).
The [18F]-fluoride ions are then eluted from the cartridge into the reaction vessel using 0.5 mL of a
solution containing Kryptofix (K222), potassium carbonate, acetonitrile and water (eluent mixture).
Note that Kryptofix is necessary in a following step to perform the nucleophilic substitution reaction.
4-5 18F azeotropic drying
After the transfer of the eluent containing the radioactivity in the reaction vessel, the solvents are
evaporated until dryness. During the drying process, a small amount of acetonitrile (100 µL) is added
to the reaction vessel. The evaporation is carried out with heating under nitrogen flow and under
vacuum.
4-6 Labelling the precursor

The mannose triflate precursor (1.7 mL) is added to the dry residue in the reaction vessel. A
nucleophilic substitution reaction occurs at 125°C in a closed environment. During the substitution,
the trifluoromethane sulfonate group of the mannose triflate precursor is replaced by the [18F] ion
and result in FTAG (2-[18F]-fluoro-1,3,4,6-tetra-O-acetyl-D-glucose).
The labelling reaction is the most critical step of the FDG synthesis. Any trace of impurity in the
incoming radioactivity, the mannose triflate precursor, the eluent mixture, the nitrogen, the QMA
cartridge or the manifold might lead to a drop of the labelling yield.
H OCOCH3 H OCOCH3
OSO2CF3 H
O Nucleophilic substitution
Nucleophilic substitution O
H3COCO H3COCO
H3COCO OCOCH3 H3COCO OCOCH3
H H H 18
F
H H H H
Mannose
Mannosetriflate precursor
triflate precursor 2-[18F]-fluo-1,3,4,6-tetra-O-acetyl D glucose
2-[18F] fluoro-1,3,4,6-tetra-O-acetyl-D- glucose
([18F]-FTAG)
18
([ F]-FTAg)
FIGURE 4-1: The nucleophilic substitution in the FDG synthesis process
4-7 Preliminary FTAG purification

In order to ensure a trapping efficiency of the FTAG of more than 95%, the acetonitrile concentration
in water should be lower than 15%. The product in the reaction vessel must therefore be diluted.
3 mL of water is added to the reaction mixture (A) in the reaction vessel. This diluted solution (B) is
further diluted in two portions. 2 mL of this solution (B) is diluted with 4.0 mL of water (C) and then
passed through the reverse phase cartridge (tC18) later used for the hydrolysis step. This operation
is done a second time with the remaining solution in the reaction vessel (D) (FIGURE 4-2). After those
19 /53
operations, the FTAG is trapped on the tC18 environmental cartridge and the solvents, unreacted 18F
ions and impurities are washed off into the external waste bottle.
Dilution in reactor Homogenised
1.6 ml ACN + 3 mL H2O
Solution A Solution B
Dilution in syringe Homogenised in syringe Trapping on tC18
2.3 mL solution B
+ 4.0 mL H2O
Solution B Solution C
Dilution in syringe Homogenised in syringe Trapping on tC18
2.3 mL solution B
+ 4.0 mL H2O
Solution B Solution D
FIGURE 4-2: Trapping of the FTAG in solution on the tC18 environmental cartridge
The reactor is rinsed twice with 3 mL of water. The rinsing solution is also withdrawn and passed
through the tC18 cartridge.
After trapping of the labelled precursor onto the cartridge, the intermediate FTAG product is pre-
purified. The cartridge is rinsed twice using 7 and 6 mL of water respectively.
4-8 Hydrolysis on solid support

The acetylated compound (FTAG) is converted into FDG by removing the 4 acetyl protecting groups.
This de-protection is carried out when the product is trapped on the tC18 environmental cartridge
through alkaline hydrolysis. The hydrolysis is performed at room temperature by means of 1 mL of
NaOH 2 N.
20 /53
H OCOCH3 H OH
H H
O Hydrolysis
Hydrolysis
O
H3COCO HO
H3COCO OCOCH3 HO OH
H 18
F H 18
F
H H H H
2-[18F]-fluo-1,3,4,6-tetra-O-acetyl D glucose 2-[18F]-fluo-2-deoxy-D-glucose
2-[18F] fluoro-1,3,4,6-tetra-O-acetyl-D- glucose 2-[18F] fluoro-2-deoxy-D- glucose
([18F]-FTAG)
([18F]-FTAg)
([18F]-FDG)
([18F]-FDG)
FIGURE 4-3: The alkaline hydrolysis in the FDG synthesis process
4-9 pH and osmolality adjustment

After hydrolysis, the alkaline FDG solution is collected in 2 mL of water and mixed up with the
neutralization solution (citrate buffer). 1.70 mL of citrate buffer are used to neutralize the FDG basic
solution.
Note that unlike the labelling intermediate, FDG is not retained on the tC18 environmental cartridge,
and can be eluted simply with water.
Duration of the step: ± 45 seconds
4-10 Purification and transfer

The resulting neutralized FDG solution is purified by passing through a tC18 plus cartridge retaining
partially hydrolysed compounds and non-polar by-products, and by passing through an Alumina N
cartridge retaining the last traces of unreacted 18F ions.
A 0.2 µm vented filter must be added at the end of the collection line as a final particle filter for the
FDG solution. Users who wish to perform subsequent sterilization procedures may need permission
from third-party patent holders.
The cassette, the cartridges and the filter are rinsed once with 5 mL and twice with 6 mL of water
in order to recover the residual FDG remaining in the lines and to drain this FDG into the final vial.
The final volume of FDG is 22 mL ± 1 mL
Duration of this step: ± 3.5 minutes
4-11 Cassette rinsing

At the end of the two runs, roughly 8% of the radioactivity is still spread over the cassette
components, as displayed on FIGURE 4-4. It is important to minimize the residual activity on the
cassette in order to have acceptable dose exposure for the operator allowing back to back
productions with different cassettes.
Following the chemical process a cassette rinsing procedure has been implemented which leads to
less than 1% residual activity.
Seven (7) elements of the cassette are washed during the rinsing process: both QMA cartridges, the
activity conical reservoir, the reaction vessel, both tC18 cartridges and the long tubing between the
right hand extremity of the cassette and the reaction vessel.
21 /53
tC18 environnemental: 1%
QMA 2: 0.2%
QMA 1: 0.2% tC18 plus: 0.5%
Long tubing: 1%
Alumina cartridges: 0.3% (each)

Activity conical Reaction
reservoir: 1.5% vessel: 2%
FIGURE 4-4: Residual radioactivity after a synthesis before the rinsing is performed.
Decay of the first run has not been considered.
At the end of the rinsing procedure, the total residual radioactivity on the cassette is reduced to less
than 1%, mainly on the tC18 environmental, the reaction vessel, and the second Alumina (which
can’t be rinsed).
Duration of the rinsing steps: ± 20 minutes
4-12 General information for one production
- Typical FDG yield (corrected for decay) : More than 80%

- Typical final volume: 22 mL ± 1 mL
- Typical duration (between radioactivity transfer and collection of the product): 30 min
22 /53
CHAPTER 5 - OPERATING TWO PRODUCTIONS ON THE SAME CASSETTE

5-1 Introduction
The FDG Duo citrate cassette has been designed to allow two back to back productions of FDG
citrate on the FASTlab 2 synthesizer. Each run from a FDG Duo citrate cassette has equivalent
quality and performance, and both productions generate separate production reports for each FDG
batch produced.
The two productions are separated by a cleaning step that ensures that the unique elements of the
cassette are cleaned appropriately and can be safely reused for the second production. This
cleaning sequence automatically takes place after the first production.
After this recycling step, the workflow progress to a waiting step, allowing the two productions to
be performed with a delay between them. This allows the two productions to be carried out back
to back, improving the quantity of FDG produced on a daily basis, or to be separated by up to 26
hours to ensure that the second production will be performed only when it is needed.
The rinsing steps can be run at the end of the workflow to wash the chemicals and most of the
residual radioactivity out of the cassette, allowing safer removal and handling of the disposable
FDG Duo citrate cassette.
Should you decide to perform the first production only; the rinsing steps can still be carried out to
ensure reduction of the residual radioactivity in every situation. Simply click the “rinsing” option
when asked by the supervision software.
5-2 Installation of the side hook for the water bag on the FASTlab 2 synthesizer
The FDG Duo citrate cassette required usage of more chemicals than the FDG citrate single run. For
this reason, all the reagent barrels on the cassette have been filled with reagent vials and the water
bag spike is not placed on the same position as usual. A small piercing device has to be placed on
the water bag puncher in order to punch the additional vial on its spike, and the water bag must be
placed hanging on a side hook on the right hand side of the synthesizer (FIGURE 5-1).
FIGURE 5-1: Additional elements to use for a FDG Duo citrate production
5-2-1 Assembly of the side hook

The pieces for assembling the side hook are packaged together within the FASTlab 2 packaging.
23 /53
Those pieces include, aside from the piercing device, a metallic support, a plastic manchon, the
hook, and 4 screws to assemble the part on the synthesizer (see FIGURE 5-2).
FIGURE 5-2: Pieces required for the assembly of the hook on the FASTlab 2 synthesizer
Required tool
An hexagonal Allen wrench (3mm)
Instructions
Start by screwing the metallic support on the right hand side of the FASTlab 2 synthesizer using the
two screws provided in the package (FIGURE 5-3)
Front Back
FIGURE 5-3: Use the two screws to assemble the metallic support
on the right hand flank of the FASTlab 2 synthesizer
Place the plastic manchon in the front facing hole of the metallic support, and slide the hook inside
it. Fasten the two pieces with the large head screws (FIGURE 5-4).
24 /53
FIGURE 5-4: Assemble the hook pieces and secure them with the large head screws.
5-3 Mount the FDG Duo citrate cassette on the FASTlab 2 synthesizer
The FDG Duo citrate cassette is slightly trickier to mount than the procedure for a single run cassette
described in the “FASTlab 2 – Operator Manual”. Please follow the procedure described below to
ensure that the FDG Duo cassette is properly mounted for a good synthesis (actions that differ from
other tracers are highlighted in bold).
1. Open the double plastic bag protecting the cassette and remove it from the hard plastic
sheet.
2. Place the individual nitrogen filter on the left-hand side connector of the manifold of the
manifold.
3. Remove the reactor, collection, and recovery water tubing from the slots in which they are
maintained.
4. Place the cassette in the open cassette drawer, and put the reactor in the left reactor
heater.
5. Press the two buttons on the synthesizer simultaneously to close the cassette drawer.
6. Verify that no tubing is squeezed or blocked between the cassette cover and the the
synthesizer.
7. Connect both collection lines to collection vials/your dispensing unit. Please don’t forget
that a 0.2 µm sterile filter must be added at the end of those lines. The collection vials should
be shielded appropriately to reduce the exposure of the operator. The line placed in position
v20 (on the lower Alumina cartridge) is the collection line for the FIRST production (blue
sleeve). The line placed in position v21 (on the higher Alumina cartridge) is the collection line
for the SECOND production (red sleeve).
8. Place the reagent vial piercing device on the FASTlab 2 water bag puncher so that the
acetonitrile vial will be automatically pierced. The reagent piercing device is an additional
spare part delivered with the FASTlab 2.
9. Connect the recovery water tube on the left of the cassette with the connector of the
recovery water vial cap. Press firmly to ensure leak-tightness of the system.
10. Verify that the waste bottle is empty as the two productions back to back will fill it with
250 mL.
25 /53
11. Manually pierce the 250 mL water bag with the water bag spike (remove the water bag
spike cap), then place the water bag on the hook on the right side of the FASTlab 2
synthesizer. The hook is an additional spare part delivered with the FASTlab 2. Please do
this operation AFTER the cassette test to avoid potential manifold contamination with
water during the test.
FIGURE 5-5: Placement of the FDG Duo citrate cassette
5-4 The workflow advancement

The two FDG Duo citrate productions are processed just as any other
production with the FASTlab 2 synthesizer. Each production consist in
several identical steps (activity loading, synthesis and tracer transfer), with
only the different integrity tests and the final cassette rinsing being run once
for the cassette.
During the production, the advancement of the process can be followed on

the left panel of the production screen (FIGURE 5-6). The current step is
highlighted in yellow and the finished steps are highlighter in green. In the
specific case of the FDG Duo workflow, the steps that are skipped for the
second production (cassette test for example) will also be highlighted in
green as they have already been performed on the cassette earlier.
For more information on the general operations for production with the
FASTlab 2, please refer to the “FASTlab 2 – Operator Manual”.
After clicking the “Tracer transfer” button at the end of the first production,
the FDG citrate will be transferred to the first collection vial, and immediately
after the cleaning process will be automatically started.
5-5 The cleaning process FIGURE 5-6: Synthesis

The cleaning process is carried on right after the end of the first production. advancement panel
These steps ensure that all the parts of the cassette have been adequately recovered for the second
production on the FGD Duo citrate cassette.
The manifold is cleaned with acetonitrile and water to remove the residual Kryptofix, potassium
26 /53
carbonate and acetonitrile residues, and the tC18 cartridges are reconditioned with ethanol,
acetonitrile and water.
This cleaning procedure takes on average 9 minutes to complete.

After the cleaning procedure, the first production ends, and the “Save” button must be pressed to
finalize the first production report. The system is now ready to run the next production, and proceed
to the waiting time between the two productions.
5-6 The waiting time

The second production can be started after the first one within 26 hours after the punching of the
reagents vials on the cassette.
The FASTlab 2 software restricts the maximum waiting to 26 hours. The maximum waiting time was
validated to ensure that the chemical stability of the cassette is appropriate to perform a second
FDG process in the same conditions and leading to the same performance and final product quality
than the first run.
When the first production is completed and saved, the synthesizer goes in a stand-by mode and
offer two options to the operator (FIGURE 5-7).
FIGURE 5-7: After the first production, the operator can choose when to start the second production.
The operator can choose to start the next production or to skip it. Skipping the second production
simply means that the workflow on the FDG Duo citrate cassette will end there, with a possibility to
rinse and empty the cassette, and that the second production will never be made with this cassette.
Please note that this operation is not reversible. A small text box will be displayed if the operator
decides to skip the synthesis in order to confirm his/her decision.
FIGURE 5-8: Please confirm if you want to skip the second production
The remaining time to start the second production is displayed on screen by a countdown timer.
When this timer reaches 0 second, it is not possible to carry on with the production, and the only
possibility is to rinse and empty the cassette before the end of the workflow (FIGURE 5-10).
To start the second production, click the “Start next synthesis” button.
Important note: Do not power OFF the FASTlab 2 synthesizer during the waiting time as the PLC
27 /53
would lose all the information needed to allow a reliable second production. If the FASTlab 2 is shut
down during the waiting time, it will not be possible to perform the second production.
5-7 The second production on the FDG Duo citrate cassette

Upon clicking the “Start next synthesis” button, the operator is prompted to enter his/her login name
and password for the second production (as the report will be specific to this production, and that
the operator might be different than the one of the first production).
FIGURE 5-9: Please enter your credential to start the second production
The sequence for the second production is automatically uploaded to the PLC, and the operator
must select the volume of radioactivity that will be delivered to the FASTlab 2 synthesizer (can be
different than the first one).
After the transfer of the second production to its collection vial, the operator is prompted to end the
workflow or to rinse the cassette (see section 4-11 of this manual).
Both options finalize the procedure, generate a production report that must be saved, and actuate
the valves and syringe drivers so that the cassette is ready to be unmounted.
FIGURE 5-10: At the end of the workflow, the operator is always asked
if he wishes to perform the cassette rinsing, or to directly end the procedure.
WARNING – It is strongly recommended to ALWAYS unmount the cassette by opening the drawer
of the FASTlab 2 synthesizer before turning the equipment off.
Upon activation of the FASTlab 2, the actuators rotate several times to reach their home central
position, which can cause residual reagents to be sent back to the recovery 18O-water vial if the
cassette is still mounted on the synthesizer.
5-8 FDG Duo citrate cassette removal after workflow

After use, the disposable FDG Duo citrate cassette contains residues of radioactive material, even
after the cassette rinsing. After the workflow, simply press the “Open drawer” button in the
maintenance mode to unmount the cassette from the FASTlab and automatically disconnect the
line to the recovery water bottle.
Do not open the hot cell or remove the cassette from the open drawer before complete decay if it
is not necessary. It is recommended to do so only before the next run.
WARNING – Always measure the remaining radioactivity before working next to the synthesizer
28 /53
after a production. Appropriate personal protection equipment must be worn at all time.
In the case the cassette has to be removed before complete decay, measure the radiation level
before the removal of the FDG Duo citrate cassette and make sure that no unnecessary radiation
exposure to the operator results from these operations.
5-9 Discarding of the cassette

The FDG Duo citrate cassette contaminated with radioactive material has to be discarded in
compliance with local radioprotection regulations. It is recommended to store it behind shielding
for at least 48 hours after synthesis.
Important note: The FDG Duo citrate cassette can also be contaminated with long half-life
radioactive target impurities especially on the QMA cartridge. It is highly recommended to remove
the cartridge from the manifold and to store it in a long-life decay lead container.
5-10 Specific troubleshooting

This chapter is dedicated to the specific FDG Duo citrate process-related troubleshooting.
This chapter is complementary with the troubleshooting chapter of the “FASTlab 2 - Service Manual”
and the chapter 9 of this manual. Altogether they are dedicated to cover the most common
problems that could occur during automated synthesis with the FASTlab 2 synthesizer.
This chapter covers the FDG Duo citrate specific process troubleshooting.
Chapter 9 of this manual covers the cassette parts and chemistry related problems.
Chapter 7 of the “FASTlab 2 - Service Manual” covers the hardware and software related problems.
WARNING – The two productions of the FDG Duo citrate workflow have been designed to label FDG
citrate in a reliable and reproducible manner. This requires both productions to be performed under
normal conditions.
In the event of a failed first production (either a synthesizer or a QC issue), the second production
must be aborted and the whole cassette must be appropriately disposed of.
after a production. Wait for sufficient decay before removing the cassette, and ensure that the
radioactivity has been located and that the cassette can be handled with minimum exposure of the
operator. Appropriate personal protection equipment must be worn at all time.
5-10-1 Liquid is coming out of the rear of the FASTlab module

The FDG Duo citrate workflow consists of two back to back production generating around 250 mL
of waste liquid sent to the waste bottle. This means that the 250 mL waste bottle should be empty
at the beginning of each FDG Duo workflow.
Otherwise the additional liquid sent to the waste bottle will be transferred out of the synthesizer by
the vacuum pump exhaust. Additionally, the vacuum pump might be damaged by the liquid.
WARNING – In such a case, the liquid may be radioactive. Please always assess the level of
radioactivity before opening the hot cell and wear Personal Protection Equipment while cleaning
the area. Wait for sufficient decay to avoid any unnecessary radiation exposure to the operator.
5-10-2 I don’t see the cassette rinsing checkbox

This is perfectly normal, and it is always possible to perform the cassette rinsing.
The FDG Duo citrate workflow differs from other tracers by the fact that one or two productions can
be performed with the same cassette. This means that the cassette rinsing might be performed
29 /53
after one or two production depending on the operator choice. To enable this possibility, the
cassette rinsing is not activated by a checkbox anymore, but will be asked for at the end of the
workflow (FIGURE 5-11).
FIGURE 5-11: At the end of the workflow, the operator is always asked
if he wishes to rinse and empty the cassette
5-10-3 I can’t start the second production

In order to reliably produce two batches of FDG with the same cassette, it is crucial that the system
knows exactly the state of the cassette before the second production (i.e. amount of reagents,
contamination of the cassette…).
This is the reason why, if the first production fails for a reason, it is strongly not recommended to
perform the second production as the starting state would be different than after a successful
production.
This also means that if the FASTlab 2 is shut down between the two productions, it will not be
possible to perform the second run upon power up. The message “Remove the cassette to start a
new synthesis” will be displayed on the screen.
Another possibility is that the time out has expired. To ensure quality and integrity of the reagent,
the second production must be carried out within 26 hours of the reagent punching at the start of
the first production. After this delay, the supervision will proceed to the end of the workflow, and
ask the operator if he wishes to rinse the cassette (FIGURE 5-11).
5-10-4 I ended the workflow after the first production, and then removed the cassette without
cleaning/emptying it. Can I reuse the cassette for another first production another day?
No.
This is both unsafe due to potential reagent contamination, and unreliable as the first run is
designed to be carried out with a new cassette.
30 /53
CHAPTER 6 - CALIBRATION OF THE RADIOACTIVITY DETECTORS

The FASTlab 2 synthesizer is equipped with 6 build-in radioactivity detectors. Those detectors are
used to estimate the production yield in the report at the end of the workflow.
Over time, the radioactivity detectors might be subjected to a slight drift. That is why calibration of
the detectors is strongly recommended to keep a good estimation of the productions yields.
Yearly calibration of the detectors is recommended if the radioactivity range remains the same. A
calibration procedure must also be performed every time the radioactivity level used for the
synthesis is changed.
Important note: Though it is recommended to perform the calibration process every year, it is not
a part of the yearly maintenance, and is not performed by GE Healthcare’s service. This operation
must be performed by the FASTlab user whenever deemed necessary.
WARNING - The purpose of the embedded radioactivity detectors from the FASTlab is to follow the
radiochemical process only. Under no circumstances can they be used to assess the radioactivity
level inside the hot cell.
The calibration procedure requires comparison of the radioactivity on most of the components of
the cassette with the radioactivity measurement done by the radioactivity detectors during the
synthesis.
As the FDG Duo citrate cassette allows the production of two batches of FDG back to back, and that
the trapping of the incoming radioactivity is made on two different cartridges, the calibration and
calculation parameters for the two productions will be different.
6-1 Calibration of the first production

Perform a first production of FDG using a FDG Duo citrate cassette and check the “single run for
calibration” box. This is MANDATORY to ensure that the first production can be used for the
calibration of the detectors, meaning that the automatic recycling and cleaning of the cassette
parts will be disabled, allowing the residual radioactivity measurement at the end of the production.
FIGURE 6-1: Please check the “Single run for calibration” box during the production in order to perform
calibration of the first production.
After this first run, the FDG duo citrate has to be removed from the FASTlab 2 synthesizer after a
timeframe sufficient enough to minimize the dose received by the operator, but short enough so
that residual radioactivity can still be measured on the different parts of the cassette.
31 /53
From the cassette, the following parts must be disassembled and placed in a plastic bag for
radioactivity counting with a dose calibrator:
- The transfer tubing – run 1

- The QMA – run 1
- The reaction vessel
- The tC18 environmental
- The Alumina – run 1
- The tC18 plus short
Please note that the following parts, not on the cassette, also have to be counted:
- The content of the waste bottle. To do so please carefully pour the liquid contained in the
waste bottle into a container that fits into the dose calibrator for the radioactivity
measurement.
- The enriched water recovery vial
- The collected FDG citrate product
- The sterile filter at the end of the transfer tubing (add this value to the “transfer tubing” value
previously measured)
Altogether, ten elements must be counted (radioactivity and reference time). Those data will be
entered into the FASTlab software as described in the “Calibration procedure” section of the FASTlab
documentation.
Important note: The “Calibration Procedure” states that it is possible to perform the calibration
procedure either for the entire tracer package, or just for a specific sequence in the tracer package.
As the two productions of an FDG Duo citrate workflow are two different sequences of a single
process, please always check the “Configure calibration for the sequence defined in the report
only” box when calibrating the FDG Duo citrate productions. Simply select the report generated
at the end of the first production run performed for calibration.
FIGURE 6-2: Always configure the calibration for the first, or second, production of the FDG Duo citrate, and to
select the fitting report (i.e. first production for calibration, or second production without the rinsing)
A small pop-up window appears and confirms that you are calibration only one of the two
production (FIGURE 6-3).
If you forgot to check the “Configure calibration for the sequence defined in the report only”, another
pop-up will warn you about that fact, so you can click “No” and check the box.
FIGURE 6-3: The pop-up window informs you that you are calibrating only one sequence (on the left), or all the
sequences in the data tracer package (on the right). Always calibrate for one sequence for FDG Duo citrate
calibration.
32 /53
6-2 Calibration of the second production

Perform both productions of FDG Duo using a FDG Duo citrate cassette with the first production
being a cold run (with no radioactivity) without the “single run for calibration” box checked, and
don’t upload the rinsing sequence (i.e. one should not perform the cassette rinsing) at the end of
both productions in order to precisely measure the residual radioactivity on the cassette.
After this second production, the FDG duo citrate cassette must be removed from the FASTlab
synthesizer after a timeframe sufficient enough to minimize the dose received by the operator, but
short enough so that residual radioactivity can still be measured on the different parts of the
cassette.
From the cassette, the following parts must be disassembled and placed in a plastic bag for
radioactivity counting with a dose calibrator:
- The transfer tubing – run 2

- The QMA – run 2
- The reaction vessel
- The tC18 environmental
- The Alumina – run 2
- The tC18 plus short
Please note that the following parts, not on the cassette, also have to be counted:
- The content of the waste bottle. To do so please carefully transfer the liquid contained in
the waste bottle into a container that fits into the dose calibrator for the radioactivity
measurement.
- The enriched water recovery vial
- The collected FDG citrate product
- The sterile filter at the end of the transfer tubing (add this value to the “transfer tubing” value
previously measured)
Altogether, ten elements must be counted (radioactivity and reference time). Those data will be
entered into the FASTlab 2 software as described in the “Calibration procedure” section of the
FASTlab 2 documentation.
The same procedure than for the first production applies. Go to the “Tools” -> “Calibration” menu,
and select the relevant report. Do not forget to check the “Configure calibration for the sequence
defined in the report only” box, to avoid overwriting the parameters calculated earlier for the
first production.
Important note: Even if the two productions have been performed, only the report of the second
one will be displayed in the list. The first production report is not usable for calibration as the “single
run for calibration” box was not checked.
33 /53
CHAPTER 7 - REPORTS
7-1 Introduction
During or after a production, a report window is available through the top menu bar. Click on the
“Report” then “Synthesis” menu entry to access the complete report menu.
The FDG Duo citrate workflow consists of three parts – run 1, run 2 and rinsing - each generating a
report. A different report will be generated for the first production, the second production, and for
the rinsing at the end of the workflow.
The synthesis report is saved in the database when the operator clicks “Save” at the end of a
production or finalizes a calibration. Always save at the end of a production before viewing or
printing its report so you can be sure it has been finalized.
A report number is automatically generated by the system. This number is displayed on the upper
right corner of the synthesis report.
Important note: The report number is generated automatically is only computer specific. This
means that if two computers are running the supervision software, their generated reports will have
the same numbers even if the production were different. Always verify both the report number AND
the computer identifier (recorded in the report) to identify a production.
The following part will describe the different information found in the synthesis report. For general
information and customisation of the report, please refer to the “Report” chapter of the ‘FASTlab –
Operator Manual”.
34 /53
35 /53
36 /53
7-2 General information

The general information at the beginning of the first page of the report is described in the following
table.
TABLE 2: Explanation of the general information contained in the report.

Field name Content
Tracer The name of the tracer that has been synthesized
The batch number of the production can be filled during
Customer batch
the production by the operator. If so, it will appear in this
number
location
Date Date of the synthesis
The name of the operator who entered its credentials at
Operator
the beginning of the production
Cassette test Name of the cassette test sequence used and unique
sequence GUID number (GE identification number)
Name of the synthesis sequence used and unique GUID
Synthesis sequence
number (GE identification number)
Synthesizer ID ID of the synthesizer used for the synthesis
Supervision software version – PLC version of the
Software version
synthesizer
37 /53
Field name Content

Identification of the workflow number. The first number is
the amount of time a production has been started on this
computer, and the second number, the sequence number
Workflow ID
in the process (please note that FDG Duo citrate is a three
sequences process – first production, second production
and cassette rinsing)
Calibration report Report number of the last calibration of the radio
number detectors for this tracer
Cassette expiry date Date of cassette expiry
Transcription of the numbers under the code bar of the
Cassette reference
cassette
Displays the name of the computer which has been used
Computer name*
for the synthesis.
* This entry appears only if the option has been selected in the settings; see “FASTlab
– Pre-Installation manual”.
7-2-1 Process report

In the process part of the report, the status of the lab unit test, the cassette test, the synthesis and
the cassette rinsing are reported as
· Synthesizer test: (Successful, Bypassed or Failed)

· Cassette test: (Successful, Bypassed, Failed or Aborted)
· Synthesis: (Not started, In progress, Successful, Failed or Aborted)
· Cassette rinsing: (Enabled or bypassed)
All the details are reported in the log table on the third page of the report.
The use or non-use of the pause and manual modes are also reported in this process report.
7-2-2 Yield summary

The synthesis report uses the calibrated radioactivity detectors of the FASTlab to calculate the yield
of the production thanks to a unique formula. The different data used for this calculation are
recorded in this part of the report. Please find a short explanation of the different fields in the TABLE
3 below.
TABLE 3: Explanation of the information contained in the report.

Field name Content
Time at reagent Time (hh:mm:ss) when the reagents have been punched
connection on the synthesizer (reagents in contact with the cassette)
Time at start of Time (hh:mm:ss) when the radioactivity has been
synthesis transferred into the synthesizer (start of synthesis)
Time at end of Time (hh:mm:ss) when the FDG is in the S3 syringe waiting
synthesis for transfer outside the cassette (end of synthesis)
Duration of the synthesis (between the time at start and
Synthesis duration
end of synthesis)
38 /53
Field name Content

Volume of the target chosen at the beginning of the
Target volume
synthesis
18F radioactivity measured by the built-in radioactivity
Starting radioactivity detector behind the QMA cartridge when the [18F]-has
been trapped on the cartridge
FDG radioactivity measured by the built-in radioactivity
Tracer radioactivity detector behind the right hand syringe when the FDG is
at end of synthesis contained in the syringe before the purification and
transfer to the collection vial.
Tracer radioactivity FDG radioactivity measured by external detector (not
at end of transfer needed for the FDG synthesis)
Final volume of tracer after transfer. This value depends
Volume of tracer on the sequence selected at the beginning of the
production
Concentration at end Calculation of the radioactivity concentration in the final
of synthesis product
Estimated Yield at
Calculation of the synthesis yield at End of Synthesis (EOS)
end of synthesis
Estimated Yield Calculation of the synthesis yield taking account of decay
decay corrected correction between start and end of the synthesis.
7-2-3 Activity trending

The graph in this section shows the radioactivity trending of the four detectors used during the FDG
Duo citrate synthesis. There are 14 checkpoints during the synthesis during which the measures
are taken, and an additional one during the cassette cleaning only for the first production.
Provided the radioactivity detectors are properly calibrated, this can be a great tool to follow the
progress of the synthesis and check the radioactivity has been handled as usual during the process.
7-2-4 Trending
The table present on the third page summarize the different radioactivity and temperature of the
reaction vessel at the check points of the synthesis.
7-2-5 Log
The log tables reports the important events occurring during the synthesis. Those events may be
information like the end of the synthesis, warning, like the impossibility to read to bar code/RFID of
the cassette, or errors like a problem of leak tightness, or a manual abort of the workflow by the
operator.
7-2-6 Operator comment

The comments that can be entered during the synthesis or just before saving the report will be
displayed in this section. Some additional space is also left in order to add any manual comment
after printing the report.
7-2-7 Operator signature

Field reserved for the handwritten signature of the operator.
39 /53
Important note: There is no possibility to digitally sign the production report via the FASTlab
supervision software. The report must be printed and completed with a handwritten signature.
7-2-8 Responsible signature

Field reserved for the handwritten signature of the production responsible.
Important note: There is no possibility to digitally sign the production report via the FASTlab
supervision software. The report must be printed and completed with a handwritten signature.
7-3 Cassette rinsing report

The cassette rinsing report is specific to the FDG Duo citrate workflow. It comprises in a short
reminder of the workflow followed during the synthesis. The report numbers of the first and, if
relevant, the second production are indicated in the middle of the page, just under the cassette
rinsing information.
The cassette rinsing information at the top of the page shows the time at the start and at the end
of the cassette rinsing, and whether the rinsing has been executed successfully, failed, or was
bypassed at the end of the workflow.
Finally, a summary of the logs of both productions can be found at the end of the document.
Please find below and example of a cassette rinsing report after the two productions have been
performed.
40 /53
41 /53
CHAPTER 8 - FDG CITRATE QUALITY CONTROL

Proper Quality Control (shortened as QC) must be performed on every batch of solution produced
using the FASTlab 2 synthesizer, in accordance with the local laws and regulations.
Systematic sterilization of the product thanks to a 0.2 µm sterile filter must be performed on the
produced FDG.
GE Healthcare takes no responsibility for the conversion of the produced radiochemical into a
radiopharmaceutical suitable for human body injection. This is solely the responsibility of the
customer and the qualified radiopharmacist on site.
Important note: It is recommended to regularly check the hand contamination of the operator
during QC work, both for safety and accuracy reasons.
Important note: The use of Personal Protective Equipment (PPE) such as safety glasses, gloves and
a lab coat is mandatory when proceeding to the QC analysis of the produced tracer. Nitrile gloves
are highly recommended when handling contaminated material, instead of latex which is more
porous.
Please handle the radioactivity behind an appropriate shielding as much as possible even during
QC testing.
The operator should wear personal dosimeter at any time while handling or working with
radioactive products.
Find below the typical FDG quality control method (fully described in the European Pharmacopeia
and in the US Pharmacopeia).
TABLE IV: Typical QC methods for FDG citrate solution

Type of Quality Control Suggested analytical methods
Radio-TLC scanner
Radiochemical purity HPLC equipped with a strongly basic anion-exchange column,
an electrochemical detector and a radio-flow detector
Radionuclidic purity* Gamma-ray spectrum recorded using a suitable instrument
Residual solvents (ethanol and
GC equipped with a FID detector
acetonitrile)
Chemical Purity Ionic chromatography
Colour spot test (Nucl. Med. Biol. Vol. 24, pp. 193-195, 1997)
Residual Kryptofix
TLC detection (Nucl. Med. Biol. Vol. 16, pp. 358-387, 1989)
pH meter
pH
pH indicator paper strips
Sterility test Proven methods
Pyrogen/Endotoxin test Proven methods
* This test is mandatory in the scope of the Quality Control
WARNING – The final product filters, not included in the cassette package, must always be tested
for integrity (commonly thanks to a bubble point test). It is recommended to validate your site-
specific process of aseptic filtration.
The typical FDG quality control values, and the acceptable range as described by the
Pharmacopeia, are shown in the table below (TABLE V).
42 /53
TABLE V: European and American Pharmacopeia specification compared with typical values obtained with
the FASTlab 2 synthesizer FDG citrate production
Type of Quality Typical FASTlab FDG
Eur. Ph. USP
control bulk QC*
Radiochemical purity > 95% > 90% > 98%
Radionuclidic purity 105-115 min 105-115 min 105-115 min

Acetonitrile < 4.1 mg/V** Acetonitrile < 0.04% Acetonitrile < 50 ppm
Residual solvents Ethanol < 5000 ppm Ethanol < 5000 ppm Ethanol < 3000 ppm
Chloro-DG < 0.5 mg/V** Chloro-DG < 0.5 mg/V** Chloro-DG < 0.1 mg/V**
Chemical purity [19F]-FDG < 0.5 mg/V** [19F]-FDG < 10 mg/V** [19F]-FDG < 0.1 mg/V**
Residual Kryptofix < 2.2 mg/V** < 50 ppm < 5 ppm
pH 4.5-8.5 4.5-7.5 6 ± 0.5

< 175 UI/mL
Bacterial endotoxins < 175 UI/mL < 175 EU/mL
< 175 EU/mL
* The typical values are simply an indication of the values usually obtained with the FASTlab 2
synthesizer. The acceptance range for the production differs from those values and can be found
in the tracer product datasheet.
** V stands for the maximum recommended injection volume (in most of the cases, 10 mL)
43 /53
CHAPTER 9 - FDG DUO CITRATE CASSETTE REMOVAL

WARNING – It is strongly recommended to ALWAYS unmount the cassette by opening the drawer
of the FASTlab 2 synthesizer before turning the equipment off.
Upon activation of the FASTlab 2, the actuators rotate several times to reach their home central
position, which can cause residual reagents to be sent back to the recovery 18O-water vial if the
cassette is still mounted on the synthesizer.
9-1 FDG Duo citrate cassette removal after production

After use, the disposable FDG Duo citrate cassette contains residues of radioactive material, even
after the cassette rinsing. After the synthesis, simply press the “Open drawer” button in the
maintenance mode to unmount the cassette from the FASTlab and automatically disconnect the
line to the recovery water bottle.
Do not open the hot cell or remove the cassette from the open drawer before complete decay if it
is not necessary. It is recommended to do so only before the next run.
after a production. Appropriate personal protection equipment must be worn at all time.
In the case the cassette has to be removed before complete decay, measure the radiation level
before the removal of the FDG Duo citrate cassette and make sure that no unnecessary radiation
exposure to the operator results from these operations.
9-2 Discarding of the cassette

The FDG Duo citrate cassette contaminated with radioactive material has to be discarded in
compliance with local radioprotection regulations. It is recommended to store it behind shielding
for at least 48 hours after synthesis.
Important note: The FDG Duo citrate cassette can also be contaminated with long half-life
radioactive target impurities especially on the QMA cartridge. It is highly recommended to remove
the cartridge from the manifold and to store it in a long-life decay lead container.
44 /53
CHAPTER 10 - TROUBLESHOOTING
10-1 Introduction and preliminary warning
This chapter is dedicated to the chemistry and quality control related troubleshooting.
This chapter is complementary with the troubleshooting chapter of the “FASTlab 2 - Service Manual”
and the chapter 5 of this manual. Altogether they are dedicated to cover the most common
problems that could occur during automated synthesis with the FASTlab 2 synthesizer.
This chapter covers the cassette parts and chemistry related problems.
Chapter 5 of this manual covers the Duo run specific process troubleshooting.
Chapter 7 of the “FASTlab 2 - Service Manual” covers the hardware and software related problems.
WARNING – The two productions of the FDG Duo citrate workflow have been designed to label FDG
citrate in a reliable and reproducible manner. This requires both productions to be performed under
normal conditions.
In the event of a failed first production (either a synthesizer or a QC issue), the second production
must be aborted and the whole cassette must be appropriately disposed of.
after a production. Wait for sufficient decay before removing the cassette, and ensure that the
radioactivity has been located and that the cassette can be handled with minimum exposure of the
operator. Appropriate personal protection equipment must be worn at all time.
WARNING – The system should be powered off before any maintenance or service intervention on
the FASTlab 2 unless the intervention requires parts to be powered on (e.g. for troubleshooting
purposes).
10-2 Low yield

Be aware that the radioactivity measurements done by the built-in detectors and the yield
mentioned in the production reports are meaningful only if the detectors are well calibrated for the
level of radioactivity used.
The measurements done by the radioactivity detectors should be considered only indicative since
the accuracy of such type of detectors is limited.
To determine the yield in the most precise manner, the starting radioactivity as well as the
radioactivity in the final solution should be measured accurately using a separate dose calibrator.
In case of a low yield, the best practice to identify the error is to identify where and under what form
the missing radioactivity is. Please note that this operation should be only performed by an
adequately trained radiochemist or similar, as it involves potential manipulation of radioactivity.
Please use the low yield fault finder, and then go to the corresponding section in this chapter:
- 10-2-1 Insufficient radioactivity trapped on the QMA cartridge

- 10-2-2: QMA elution problem
- 10-2-3: Trapping issue
- 10-2-4: Hydrolysis issue
- 10-2-5: Radiochemistry problem
Low yield default finder
45 /53
10-2-1 Insufficient radioactivity trapping on the QMA cartridge
10-2-1-1 The radioactivity was not trapped properly on the QMA cartridge and a large amount of
radioactivity is in the 18O enriched water recovery vial
This scenario can be explained by:
1. A defective QMA cartridge assembled on the cassette. In this case, wait for sufficient decay
before opening the hot cell, then start a new workflow with a new cassette.
2. A high level of impurities in the irradiated 18O water, either target impurities or residual
impurities remaining in the recycled water from a previous production.
Important note: For bombardment within the cyclotron target, the use of 18O-water enriched above
95% is recommended. Commercially available 18O-water does not usually require further
purification.
Following irradiation, the irradiated 18O-water should be colourless and free if any visible
contamination, with conductivity below 10 µS/cm (recommended). The volume of irradiated 18O-
water sent to the FASTlab 2 synthesizer should be within the range of 0.5 to 5 mL for regular
synthesis sequences.
GE Healthcare makes no guarantee regarding the presence in the final product of radio
contaminants from the target because such impurities are site related (main contributing factors
are the cyclotron and target maintenance, the quality of the enriched water and the irradiation
parameters).
Important note: GE Healthcare makes no guarantee regarding the performance of the FDG
process if the cyclotron is not operated and maintained following supplier specifications.
10-2-1-2 The radioactivity was not trapped properly into the QMA cartridge and the amount of
46 /53
recovered 18O water is much lower than the target volume sent to the FASTlab 2
This is the result of the impossibility for the radioactivity delivered by the cyclotron to flow properly
through the QMA cartridge to the water recovery vial:
1. The inlet radioactivity tubing might not be well connected to the plunger. In this case, wait
for sufficient decay before opening the hot cell and properly connect the tubing.
2. The inlet radioactivity tubing might not be leak tight anymore, or has been damaged and
kinked. Please follow the replacement procedure described in the FASTlab 2 – Service
Manual for maintenance of this part.
3. An incorrect volume has been selected at the start of the production, and a portion of the
radioactivity has been sucked to the waste bottle via the radioactivity plunger.
4. The “Activity Received” button has been clicked before the complete transfer of the 18F to
the FASTlab 2 synthesizer.
5. The tube for water recovery located on the first valve on the left of the manifold might be
squeezed (for example between the front face of the module and the hard cassette cover).
In this case a part of the enriched water will not pass through the cartridge during the
trapping step, and will remain in the conical reservoir.
6. The QMA (light blue ring) cartridge is blocked because of impurities coming out of the target.
A dark residue might be noticed on the QMA cartridge after the synthesis and some liquid
may have been left in the conical reservoir, unreacted.
7. The QMA cartridge is defective and clogged/blocked. In this case, the amount of recovered
water can be abnormally low, or there will be some liquid in the reservoir above the
cartridge after the synthesis, consisting of target water mixed with eluent.
8. The radioactivity plunger might not be leak tight anymore. Please check the radioactivity
plunger integrity by following the instructions described in the FASTlab 2 – Service Manual,
and change the rubber O-ring if appropriate.
10-2-2 QMA elution problem

Such event can happen if the eluent vial is not properly pierced, or if something prevents the eluent
withdrawal:
1. Verify that the correct level of eluent has been withdrawn from the vial at the end of the
production and that there is no leak in the elution system.
2. Verify that the spike properly pierced the eluent vial
3. Verify that the 1 mL syringe piston is hooked as intended in its driver
10-2-3 The radioactivity was not trapped properly on the tC18 cartridge before the
hydrolysis
After the labelling step, the newly synthesized FTAG is diluted with water and trapped on the tC18
cartridge. There are several reasons that could explain a bad trapping of the radioactivity on this
cartridge, and to identify the origin of the problem, it is strongly recommended to analyse the
content of the waste bottle by Thin Layer Chromatography or by radio-HPLC, after waiting for
sufficient decay to do so safely.
47 /53
10-2-3-1 There is a large amount of FTAG or FDG in the waste bottle

This means that the labelled compound failed to be trapped on the tC18 cartridge and can be
explained by different reasons;
1. There is no water bag, or the water bag is not connected properly to the cassette. This would
obviously also lead to a lower amount of solution in the final vial
2. The acetonitrile vial has not been pierced properly, or a part of the septum obstructs the
spike, preventing the good conditioning of the cartridge.
3. The tC18 cartridge is defective or not adequately filled.
4. The trapping occurred at a room temperature higher than 35°C. It is always highly
recommended to use the system in normal usage conditions (between 5 and 30°C with a
less than 80% relative humidity
10-2-4 Hydrolysis issue

The main part of the labelled solution has been successfully trapped on the cartridge, but the
hydrolysis reaction was incomplete.
This may also lead to a higher amount of partially hydrolysed compounds in the FDG solution (other
than 18F—ion).
1. The spike did not pierce properly the septum of the sodium hydroxide vial or a piece of
rubber from the stopper is blocking the spike. Verify that the correct level of sodium
hydroxide has been withdrawn from the vial at the end of the production and that there is
no leak in the hydrolysis system.
2. There is no water bag, or the water bag is not connected properly to the cassette. This would
obviously also lead to a lower amount of solution in the final vial.
3. This may be related to non-conformity of the cassette or reagent.
10-2-5 Radiochemistry problem (Labelling or drying)
10-2-5-1 The main part of the radioactivity in the waste bottle is in 18F- form
This means that the mannose triflate precursor was not properly labelled and that the main fraction
of the radioactivity is still in the 18F- form after labelling and is not retained on the tC18 cartridge.
Different reasons can explain a failed labelling step using the FASTlab 2 synthesizer:
1. Impurities or moisture in the nitrogen.
2. Impurities or moisture in the different reagents in the cassette.
3. The transfer line between the cyclotron and the FASTlab 2 has not been rinsed or replace
frequently, leading to high levels of impurity in the incoming radioactivity. The transfer lines
should be rinsed and dried after every production, and should be replaced at least on a
yearly basis to ensure good quality of the radioactivity provided to the FASTlab 2.
4. The vial piercing device has not been placed on the FASTlab 2, and the acetonitrile vial has
not been automatically pierced. This prevents a good evaporation in the reactor which
negatively affects the labelling yield.
48 /53
5. The spike did not pierce properly the septum of the mannose triflate precursor vial (orange
cap). Please verify the amount of residual mannose triflate in the vial after the production.
6. The cassette was handled with wet hands (water, isopropanol, ethanol) and its manifold has
been contaminated with it during mounting on the FASTlab 2 synthesizer.
7. The amount or the quality of the reagents is not correct.
8. There is a substantial amount of impurities coming out of the target lines in the irradiated
water, inhibiting the labelling synthesis.
9. The reactor inlet or outlet tube are (partially) squeezed or clogged between the cassette
cover and the front face of the synthesizer.
10. One of the connector on the reaction vessel is (partially) unscrewed.
11. An inert gas other than nitrogen is used.
12. The bottom or the sides of the reaction vessel is not in contact with the heater, leading to a
poor heat transfer and an incomplete reaction.
13. Verify the accuracy of the reactor heater according to the procedure described in the
FASTlab 2 – Service Manual.
10-3 Fluctuating yields

Isopropanol is commonly used to sterilize the inside of the hot cell. Accidental contamination of the
cassette and/or reagents with it may lead to yield fluctuation between productions.
10-4 Low, or fluctuating, volume of FDG in the final solution

Several factors may contribute to this situation.
1. There is no water bag or the water bag is not connected properly to the cassette preventing
water withdrawal by the water bag spike.
2. The hydrophobic nitrogen inlet filter is connected to the outlet tubing instead of a 22 µm
filter (hydrophilic membrane), so the line is blocked. In such a case, one of the silicone tubing
may pop out of its barb fitting, leading to a potential radioactivity leak onto the synthesizer.
3. A silicone tube is squeezed between the front panel of the FASTlab 2 synthesizer and the
cassette cover, preventing fluid movement in the cassette. In such a case, one of the silicone
tubing may pop out of its barb fitting, leading to a potential radioactivity leak onto the
synthesizer.
This should be detected during the cassette tests.
4. A silicone tube is partially damaged and is not leak tight anymore.

5. The tC18 plus short cartridge or the alumina N cartridge used for the final purification is
defective or blocked (this happen very rarely), causing abnormally high back pressure.
6. The buffer vial has not been properly pierced, and the citrate buffer failed to be withdrawn
and transferred to the right hand syringe during the production. In such a case, the vial is
49 /53
still filled with liquid at the end of the process, and the pH of the [18F]-FDG solution is too
high.
7. There is an extension line mounted on one of the outlets of the cassette (to a dispensing
unit for example), and the inner diameter of this extension line is too narrow, leading to high
backpressure and potential leaks.
unit for example) and the 0.2 µm filter is not mounted at the end of this extension line, but
between the cassette outlet line and the extension. The gas used to flush the FDG solution
through the line is removed by the filter, and FDG might then remain stuck in the extension
line and not been pushed into the vial/dispensing unit.
unit for example) and some FDG solution leaks away from the connections between the line
and the cassette and/or the 0.2 µm filter.
10. The waste bottle is full.
11. The cassette is not properly mounted on the FASTlab 2 synthesizer.
12. The operator is waiting too long before transferring the FDG out of the cassette. In case of
a very high radioactivity production, radiolysis may occur in the concentrated solution,
lowering the production yield.
13. The temperature inside the hot cell is too high (above 35°C), which can lead to a lower
trapping efficiency of the FTAG compound on the tC18 cartridge.
10-5 The quality of the final product does not meet the pharmaceutical requirements
10-5-1 The pH of the product is too high

In that case, the [18F]-FDG solution may also be slightly yellow. Several factors can contribute to a
higher pH of the solution. Please verify the following points:
1. The amount of sodium hydroxide used for the hydrolysis is incorrect. Please check if the
spike properly pierced the septum of the NaOH vial (red cap).
In this case, the amount of residual sodium hydroxide in the vial is lower than usual after
production.
2. Verify the expiration date of the cassette and its storage conditions as a deterred quality
NaOH may cause higher pH in the final product.
3. The buffer solution was not transferred properly into the right hand syringe during the
production.
In this case, the amount of residual sodium hydroxide in the vial is higher than usual.
10-5-2 The pH of the product is too low

A low pH is often related to an incomplete hydrolysis due to missing sodium hydroxide. In this case,
the [18F]-FDG solution may contain some non- or partially hydrolysed [18F]-FTAG, and the yield of
the production may be affected.
Please verify the amount of residual sodium hydroxide in its vial after synthesis.
50 /53
10-5-3 The FDG solution is not clear and colourless
10-5-3-1 The FDG solution is cloudy

White particles in suspension can be observed if no 0.2 µm filter has been used to filter the final
product, or if the filter is defective. Such a cloudy [18F]-FDG solution can be recovered by a second
filtration through a 0.2 µm filter, and complete quality control must then be conducted on the
filtered product.
10-5-3-2 The FDG solution is yellowish

This may result from an improper purification through the tC18 cartridge in the case where the
solution was not properly neutralized with sodium hydroxide, leading to a high pH.
10-5-4 There are unknown radioactive impurities in the FDG solution

Some impurities are commonly produced during a [18F]-FDG production on the FASTlab 2
synthesizer, including:
- Free 18F ions – less than 2% in the final solution
- [18F]-FTAG – less than 0.5% in the final solution
- Partially hydrolysed [18F]-FTAG – less than 0.5% in the final solution
No [18F]-FDM is produced by epimerization of [18F]-FDG under alkaline conditions at room

temperature.
If abnormally high amounts of non- or partially hydrolysed [18F]-FTAG are detected in the FDG
solution, this may indicate that the hydrolysis did not quantitatively occur because of some missing
sodium hydroxide.
If other unknown radioactive compounds are detected in the solution, this may have resulted from
the analytical method used for the quality control, or from a contamination of the sample or the
test equipment. In cases where the radiochemical purity is measured by Thin Layer
Chromatography (TLC), the TLC strips should not be dried at an elevated temperature after spotting
the sample just before migration to avoid degradation of the [18F]-FDG that would be also detected.
10-5-5 The amount of residual free 18F ions is abnormally high

18F- ions which did not label the precursor are drained to the waste bottle during the pre-purification
steps before the hydrolysis. The last traces of 18F- ions should be retained on the alumina N
cartridges. Therefore the amount of residual 18F- ions in the solution is generally below 2%. However,
with increasing specific radioactivity concentrations of [18F]-FDG there are increasing effects from
auto radiolysis and free radical formation which may result in rising levels of free fluoride ion over
time in the [18F]-FDG solution.
10-5-6 The amount of acetonitrile is too high

There are two possibilities when the amount of acetonitrile in the final product is too high:
1. The water bag is not properly punched: there is not enough water for rinsing the tC18
cartridge after the trapping of the FTAG. In this case, the yield and the final volume should
also be lower than expected.
2. The cassette used is too old. If the cassette is out of date, some leakages could appear from
the stopcocks, which can generate acetonitrile residue in the final product.
51 /53
10-5-7 The amount of ethanol is too high

Ethanol is used to condition the tC18 Plus short cartridge. The cartridge is then rinsed with water. A
higher amount of ethanol in the final [18F]-FDG solution means often means that the amount of
water used for the rinsing is lower than usual and is then often linked with a lower final volume as
the water withdrawal may have been hindered for the whole production.
52 /53
About GE Healthcare
GE Healthcare provides transformational
medical technologies and services that are
shaping a new age of patient care. Our broad
expertise in medical imaging and information
technologies, medical diagnostics, patient
monitoring systems, drug discovery,
biopharmaceutical manufacturing
technologies, performance improvement and
performance solutions services help our
customers to deliver better care to more people
around the world at a lower cost. In addition, we
partner with healthcare leaders, striving to
leverage the global policy change necessary to
implement a successful shift to sustainable
healthcare systems.
Our “healthymagination” vision for the future
invites the world to join us on our journey as we
continuously develop innovations focused on
reducing costs, increasing access and
improving quality and efficiency around the
world.
GE Healthcare
3000 North Grandview Blvd
Waukesha, WI 53188
U.S.A.
www.gehealthcare.com
GEMS PET Systems AB

Husbyborg
SE-75228 Uppsala,
Sweden

FDG-C Duo Application Manual

Uploaded by

Document Informationclick to expand document informationFDG duo Fastlab 2

Document Informationclick to expand document information

Copyright:

Available Formats

FDG-C Duo Application Manual

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

FDG-C Duo Application Manual

Uploaded by

Copyright:

Available Formats

GE Healthcare

Original User Instructions

FDG Duo citrate

Warranty and liability

Internet updates: Common Documentation library

ПРЕДУПРЕЖДЕНИЕ Това упътване за работа е налично само на английски език.

UPOZORENJE Ovaj servisni priručnik dostupan je na engleskom jeziku.

VÝSTRAHA Tento provozní návod existuje pouze v anglickém jazyce.

ADVARSEL Denne servicemanual findes kun på engelsk.

WAARSCHUWING Deze onderhoudshandleiding is enkel in het Engels verkrijgbaar.

FIGYELMEZTETÉS Ezen karbantartási kézikönyv kizárólag angol nyelven érhető el.

AÐVÖRUN Þessi þjónustuhandbók er aðeins fáanleg á ensku.

AVVERTENZA Il presente manuale di manutenzione è disponibile soltanto in lingua inglese.

경고 본 서비스 매뉴얼은 영어로만 이용하실 수 있습니다.

BRĪDINĀJUMS Šī apkopes rokasgrāmata ir pieejama tikai angļu valodā.

ĮSPĖJIMAS Šis eksploatavimo vadovas yra tik anglų kalba.

ADVARSEL Denne servicehåndboken finnes bare på engelsk.

OSTRZEŻENIE Niniejszy podręcznik serwisowy dostępny jest jedynie w języku angielskim.

AVISO Este manual de assistência técnica encontra-se disponível unicamente em inglês.

ATENÇÃO Este manual de assistência técnica só se encontra disponível em inglês.

ATENŢIE Acest manual de service este disponibil doar în limba engleză.

ОСТОРОЖНО! Данное руководство по техническому обслуживанию представлено только на

UPOZORENJE Ovo servisno uputstvo je dostupno samo na engleskom jeziku.

UPOZORNENIE Tento návod na obsluhu je k dispozícii len v angličtine.

ATENCION Este manual de servicio sólo existe en inglés.

VARNING Den här servicehandboken finns bara tillgänglig på engelska. .

OPOZORILO Ta servisni priročnik je na voljo samo v angleškem jeziku.

DİKKAT Bu servis kılavuzunun sadece ingilizcesi mevcuttur.

ACRONYMS & GLOSSARY

CHAPTER 6 - CALIBRATION OF THE RADIOACTIVITY DETECTORS 31

The “FASTlab 2 – User Documentation” package consist of four manuals:

- FASTlab 2 – Operator Manual

- FASTlab 2 – Service Manual

- FASTlab 2 – Pre-Installation and Installation Manual

- FASTlab 2 – Health, Safety and Regulatory Manual

CHAPTER 2 - RADIOPHARMACEUTICAL REQUIREMENTS

CHAPTER 3 - FDG DUO CITRATE CASSETTE

Mannose Sodium Citrate

CHAPTER 4 - DESCRIPTION ON THE CHEMICAL PROCESS

Tracer Package 1.0.0.1 contains:

Large target volume sequence

4-1 Preparation of the fluorinating agent

4-2 Synthesizer and cassette test

4-3 Preliminary steps

Duration of this step: ± 5 minutes

4-4 Enriched water recovery and elution

Duration of this step: ± 4 minutes

4-5 18F azeotropic drying

Duration of this step: ± 9 minutes

4-6 Labelling the precursor

Duration of this step: ± 2 minutes

4-7 Preliminary FTAG purification

Dilution in reactor Homogenised

1.6 ml ACN + 3 mL H2O

Dilution in syringe Homogenised in syringe Trapping on tC18

Dilution in syringe Homogenised in syringe Trapping on tC18

Duration of this step: ± 3 minutes